Bracing for Bioterrorism: The Push to Prepare



UAB Magazine By Russ Willcutt
Photography By Marc Bondarenko and Steve Wood
From UAB Magazine, Winter 2002 (Volume 22, Number 1)




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“When we first learned of the attack, we were in our hotel in Brooklyn, near the foot of the bridge. Thousands of people were streaming over the bridge from Manhattan, most of them covered with a gray, powdery dust,” says Thomas E. Terndrup, M.D. “We did what we could to help people there, but at some point we decided—without actually saying anything—that we needed to get closer. So we started making our way across the bridge, against the flood of people who were trying to get away from the site of the attack.”

Terndrup, who is chair of the UAB Department of Emergency Medicine and director of UAB’s Center for Disaster Preparedness (CDP), speaks calmly as he recalls his experience in New York on September 11, just after the World Trade Center towers were attacked. He was in the city attending a conference, along with Sarah McNutt, M.D., a UAB emergency medicine physician, and paramedic Shannon Stephens. When the three emergency health professionals saw the stream of injured people, their natural instincts drew them into the streets.

Throughout the rest of the day, Terndrup, McNutt, and Stephens worked at triage stations, rinsing debris-filled eyes and essentially providing “extra hands” for New York City firefighters, police officers, and emergency response personnel.

The experience, Terndrup says, brought into sharp focus the willingness of community professionals, such as those in New York, to do whatever is necessary and make sacrifices to help others in need. It also brought home some of the realities of a full-scale, terrorist-triggered human disaster—something he and his colleagues at the CDP have been studying and preparing for throughout the past couple of years.

Understanding the Unthinkable

As an emergency medicine specialist, Terndrup is acutely attuned to the consequences of disasters of all kinds—from catastrophic illness to traumatic injury. But he became particularly focused on the impact of large-scale disasters in 1999, about a month after he arrived at UAB. His interest was stirred by a call he received from an FBI agent, who asked him if anyone at UAB was working on developing mechanisms for rapidly identifying anthrax spores.

“I had no idea,” Terndrup says. “But after a few phone calls, I discovered that quite a few scientists at UAB were hard at work in that very area. I was struck by the fact that anthrax was an issue of intense international concern—even two years ago—and that it was the focus of research being conducted by many people at UAB.”

Terndrup decided to begin pulling together a network of experts on bioterrorism, from UAB and beyond, to study the emerging threat of anthrax and other biological agents. Within six months, he was deep into discussions with representatives of five UAB schools, as well as scientists from the UAB-affiliated Southern Research Institute (SRI) and Samford University’s McWhorter School of Pharmacy. By June 2000, the university system’s board of trustees had officially approved establishing the CDP.

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“I wanted to surround myself with smart people from a variety of disciplines who could bring to the table clinical perspectives, medical response perspectives, public health perspectives—anyone and everyone who could address the issue of responding to the threat of bioterrorism,” Terndrup says.

In the two years since the CDP was founded, Terndrup has assembled an impressive group of professionals from a wide variety of disciplines, including emergency medicine, biodefense, public health, microbiology, and pharmacology. The CDP’s overall commitment is to “preparedness” for all kinds of disasters—whether inflicted by terrorists or by nature—but its major focus so far has been bioterrorism.

“We chose that focus because a lot of work had already been done to prepare for disasters such as fires, tornadoes, and chemical spills, but there was a sense that we were not prepared for something like the release of biological agents by hostile forces,” Terndrup says.

Stolen Security

Today, with shock and grief over the World Trade Center disaster compounded by anxiety about the anthrax attacks that have occurred across the country—and with fears mounting about other biological and chemical agents—the question of the release of harmful substances by hostile forces is no longer hypothetical. Given the harsh new reality of terrorism inside the United States, how are experts in UAB’s Center for Disaster Preparedness addressing the new threat, and what reassurances can they give the average American, whose sense of security has been stripped away by recent atrocities?

According to David R. Franz, D.V.M., Ph.D., vice president of SRI’s Chemical and Biological Defense Division and deputy director of the CDP, the most important message for health professionals and the media to communicate to the public is simple: Don’t panic.

“Right after the terrorist attacks in New York, people began running out and buying gas masks,” he says. “But that’s just not a rational thing to do. How would you even know when to put one on? I myself don’t own a gas mask.

“We saw a similar kind of panic last fall about anthrax, with people rushing out and pleading with their physicians to give them antibiotics. That’s not reasonable, because only a small number of people have actually been exposed, and the mass use of antibiotics could create additional problems—shortages for those who really need them, for example, and, even more frightening, the emergence of drug-resistant strains.”

Allaying Alarm

A former colonel in the United States Army, Franz has studied chemical and biological terrorism for many years. He has served as commander of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and was chief inspector on three United Nations biological warfare inspection missions to Iraq at the conclusion of the Persian Gulf War, among other related assignments.

Today, Franz works with trainees at the Department of Justice’s Center for Domestic Preparedness in Anniston; he also teaches first-responders, such as police officers, paramedics, and firefighters throughout the country the best ways of dealing with biological and chemical agents. Throughout all of his educational efforts, he urges his audiences—especially the media—to understand the technical issues and to avoid panic.

“I remember some years back an anti-Semitic group left a petri dish containing a red, jellylike material at a B’nai B’rith center in Washington, D.C.,” he says. “The group claimed it was something dangerous, and since the first-responders had no experience with such things, they panicked, closing down entire city blocks and showering people off in the streets. I was following all this on television, and when I saw a banner across the bottom of the screen reading ‘Chemical Attack on D.C.!’ I knew it was time to do something to educate the media.

“Anyone who goes through the course at Anniston knows that chemical agents are neither volatile nor are they dermally active, and the vast majority of biological agents could’ve been handled by placing a wet towel over the dish and pouring bleach into it.”

Franz has since conducted numerous seminars specifically geared toward broadcast and print journalists. “Everyone I’ve met has had a sincere desire to learn how to handle these situations better,” he says. “The journalist who understands these issues can make a real contribution, not only to deterrence but also to the response process. And the one who doesn’t can have a very negative impact on our ability to protect the public.”

Enlisting Experts

One CDP member who has been quoted frequently by the media is Ken Alibek, M.D., a former Soviet scientist who is known worldwide as a top expert on biological agents. Alibek is also president of Advanced Biosystems, Inc., a subsidiary of Hadron, Inc., which is devoted to research and development of medical defenses against biological weapons.

As the former first deputy chief of Biopreparat, the civilian arm of the Soviet Union’s biological weapons program, Alibek oversaw the efforts of some 40,000 scientists charged with developing biological weapons of mass destruction. Since defecting to the United States in 1992, he has helped the government in its efforts to eliminate the danger of biological weapons—even addressing Congress on terrorist and intelligence operations in 1998.

Great strides in dealing with the threat have been made in recent years, according to Alibek. “In the past six or eight years, our preparedness for biological attacks has changed considerably for the better,” he says. “Heightened awareness of the biological threat has led to a number of positive developments—such as the creation of extensive databases on biological weapons, the development of detection equipment, analysis of possible attack scenarios and their consequences, and training for those who would serve as first-responders in case of an attack.”

Despite these advances, Alibek is convinced that the solution to the preparedness dilemma will be found in medical interventions. “Years of research on the medical aspects of biodefense have resulted in three major responses—treatment prior to exposure using vaccination, prophylactic treatment after exposure but before symptoms arise, and chemotherapy after the onset of the illness,” he says. “In my opinion, post-exposure prophylactic treatments hold the most hope. In the case of anthrax, for instance, we should devote our resources to finding ways to prevent the disease from occurring after exposure, since the main cause of death is the release of toxins into the body.

“Since the primary goal of developing bio-defense is to save human lives, we must greatly increase our efforts to develop new treatment and urgent prophylaxis techniques,” Alibek says. “Such efforts, as well as the funds spent on research and development, will pay for themselves many times over.”

Preparing for the Possibilities

According to Franz, experts such as Alibek are key to the CDP’s agenda of addressing biological threats—and that’s why he has sought to assemble a network of specialists who can collaborate on strategies. “My role in the center is really to bring people together,” he says. “Biodefense is a fairly small community, and after spending 27 years in the military, I know almost everybody in the neighborhood.”

One longtime resident of that neighborhood, says Franz, is UAB epidemiologist Michael Maetz, V.M.D., M.P.H., who serves as associate director of the CDP’s Public Health Surveillance Unit. As chair of the Department of Epidemiology and International Health in the UAB School of Public Health, Maetz is an important link between the CDP and the Alabama Department of Public Health.

A specialist in the spread of disease, Maetz was one of the first people Franz thought of when, some time ago, he was approached by an Armed Forces Medical Intelligence Agency colleague who was seeking experts to examine the human factors associated with an outbreak of plague. “With Mike and other experts from Dartmouth and MIT, we were able to assemble a team to examine the epidemiology of plague,” says Franz. “As a result, we’ve submitted a proposal to the Army to create a computer model of a plague outbreak. Most interestingly, this same model would apply to other biological agents, such as anthrax and smallpox.”

A couple of years ago, Maetz was integral to Alabama’s efforts to secure a grant from the Centers for Disease Control and Prevention (CDC) to establish a bioterrorism preparedness and response plan. “The CDC grant funds several projects—including epidemiologic monitoring, setting up a biological laboratory, and creation of the Health Alert Network, which is a communications and training system for public health personnel and health care providers throughout the state,” says Maetz. “The part I’m responsible for focuses on developing a state public health bioterrorism preparedness plan.”

Working with Maetz on this project is an advisory council with representatives from more than 35 entities, such as the state medical association, public-health agencies, the FBI, and the media, including television stations and newspapers. “We’ve met roughly twice a year to develop and draft the plan,” he says. “We’ve tried to come up with a concise, working document that can be reviewed regularly and revised as needed.

“Once the plan has been finalized and approved,” says Maetz, “it’s something we’d like to see in the hands of first-responders such as fire, police, and rescue units, and also local health departments and hospital personnel, particularly emergency room and infection control people.”

Managing the Microbes

While Franz, Maetz, and others in the CDP work to devise strategies to prepare for broad-scale bioterroristic attacks, scientists in the center’s Disease Agent Research Unit are focusing their efforts on the tiny, invisible instruments of bioterrorism—the microbes themselves.

Suzanne Michalek, Ph.D., associate director of the unit, says that the unit’s strength—like that of the center as a whole—lies in its ability to bring together scientists from many disciplines who can share ideas and findings about destructive microbes.

One such scientist is Larry DeLucas, O.D., Ph.D., director of the UAB Center for Biophysical Sciences and Engineering (CBSE), who is working on methods for detecting and disarming anthrax. One of the most promising avenues he’s pursuing—and an approach that fits perfectly with Ken Alibeck’s strategic vision—is a drug that’s being developed with funding from the U.S. Army. “This is a drug that stops anthrax at a much earlier stage than any of the antibiotics you’re hearing about now,” says DeLucas. “It works on a protein that’s critical for the germination of anthrax spores—which leads to the release of toxins into the body. If you can stop the spores from proceeding to this vegetative state, then you’ll never have to worry about anthrax harming you—whether it’s the inhaled or the cutaneous form.”

Although CBSE scientists haven’t yet arrived at the drug’s final form, DeLucas believes it may one day be used prophylactically—“as long as there aren’t too many side effects,” he notes. “But even if it does produce side effects and can only be taken post-exposure, it will still be a very fast-acting and effective drug.”

DeLucas says that in addition to developing anti-anthrax drugs, CBSE members are designing devices that will detect anthrax in the environment. For example, structural biologist Christie Brouillette, Ph.D., and engineer Ken Banaziewicz, along with UAB physicist Sergey Mirov, Ph.D., are working on a “suitcase-sized” anthrax detector. “Basically, it sucks in liters of air, processes the air, and then detects anthrax based on a chemical interaction between proteins on the surface of anthrax spores and compounds that we’ve developed for the device,” DeLucas explains.

Military Molecules

Conducting related studies are UAB microbiologists Charles Turnbough, Ph.D., and John Kearney, Ph.D., who are developing molecules that will be used by the military to detect anthrax. “Other scientists are designing the actual instrumentation,” Kearney notes. “Our job is to equip the instruments with easily detectable molecules that will bind specifically to anthrax spores.”

The molecules Kearney works with are monoclonal antibodies that are formed as part of an immune response to anthrax. To obtain he antibodies, he exposes mice to “safe” forms of anthrax and then, when the mice begin generating antibodies, he attaches fluorescent “tags” to the antibodies to isolate them. These molecules are then incorporated into an air-sampling device. “If anthrax spores are present in samples, the antibodies attach to them,” Kearney explains, “and you can see that happen because of the fluorescent tags. Used correctly in very simple devices, these antibodies could detect anthrax quickly at the front lines of an outbreak.”

Turnbough’s approach is similar, although he focuses on peptides, which are much smaller and hardier than antibodies. “Our hope is that peptides will be more robust and will be able to survive in harsher environments,” he says. “In addition, it’s possible that smaller peptides can be incorporated into different detection platforms more easily than antibodies, which are chemically fragile under certain circumstances.” Turnbough notes that the molecules that he and Kearney are developing can be incorporated into several different kinds of spore-detecting devices—including optical, electrical, and even acoustical detectors.

In addition to his work on spore detection, Turnbough and his colleagues are battling anthrax on other biological fronts.
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“We are working with Dr. De-Chu Tang at Vaxin, Inc., to develop a noninvasive DNA-based vaccine,” he says, “and my lab is identifying sites on the anthrax spore surface that we could block, thereby sabotaging its viability and virulence.”

Victory with Vaccines?

Several scientists in the CDP’s Disease Agent Research Unit are working on vaccines that could actually keep people from becoming infected by biological agents. Michalek’s own research on a vaccine for equine encephalitis—funded by a grant from the U.S. Army—is applicable to defending against any airborne contaminant.

“My work deals mainly with the mucosal membranes, so I’m interested in what happens with anything we inhale or ingest,” she says. “If you think about it, those surfaces are our first line of defense, and that’s especially important when it comes to agents of biological warfare.”

Another CDP scientist, infectious disease specialist Mark Mulligan, M.D., who directs the Alabama Vaccine Research Center at UAB, has just received a $4.3-million grant from the CDC to test an FDA-approved anthrax vaccine. “What’s currently in use by the military is a vaccine that’s administered in six injections over an 18-month period, with annual booster shots after that,” he says. “As you can imagine, keeping track of such a schedule is very difficult for a highly mobile military force. So we’re doing a clinical trial that will attempt to take the existing vaccine and alter the injection schedule to make it more ‘user-friendly,’ if you will. We’re hoping to go as low as three injections in the first 18 months, followed by boosters every two or three years. Preliminary data prepared by the Department of Defense (DOD) suggest that lower doses produce the same level of antibodies, so we feel that our chances of altering the schedule are pretty good.”

Mulligan’s work also focuses on the manner in which the vaccine is injected. “It’s currently injected under-the-skin, unlike most vaccines, which are injected straight into the muscle of the arm. The body tolerates intramuscular injections much better than subcutaneous, or under-the-skin, injections,” he says. “Again, initial DOD studies have shown that the intramuscular injection method produces just as many antibodies as the subcutaneous method.”

While the vaccine is currently available only to the military, Mulligan says that recent events may lead to increased supplies and civilian rationing. “When the supply becomes available, decisions will have to be made about whether the vaccine should be given to postal workers and fire, police, and emergency medical personnel,” he says. “In this new world we’re living in, with a war being fought right here on the homefront, there’s certainly the chance that anthrax vaccines will be used more broadly at some point.”

Even if vaccines are developed for these agents, however, Michalek says that mass producing, storing, and distributing vaccines will present formidable challenges. “People tend to think that, if a vaccine exists, then large quantities should be available, but that’s not necessarily the case,” she says. “If we do develop a vaccine for a particular agent, we’d need to determine exactly how much of a threat that agent is in order to decide how much vaccine to produce. Then, where would it be stored? What about shelf life? And who would manufacture it?

“The CDC and the military really aren’t in the business of manufacturing, storing, or distributing medications, so you’d have to find a company willing to make the vaccines, and that would be a pretty major commitment for any profit-based business. A drug company would have to be willing to go out on a limb to agree to produce most vaccines in large quantities.”

Drug Distribution Dilemmas

Distribution of drugs to treat bioterrorism-caused diseases is the focus of yet another CDP unit—the Pharmaceuticals Preparation Unit, headed by Susan Alverson, D.P.A., assistant dean of Samford University’s McWhorter School of Pharmacy.

According to Alverson, fluctuations in the demand for certain medications could actually serve as harbingers of disease outbreaks associated with biological warfare.

“The biological agent at the top of most everyone’s list is anthrax, which resembles the flu in its earliest stages,” says Alverson. “So pharmacists would really be in an excellent position to notice a rise in people getting medications for flu-like symptoms or people who are experiencing such symptoms at an unlikely time of year, like early summer.”

Pharmacists can also detect outbreaks by keeping a close watch on inventory levels of certain drugs, Alverson says. “Pharmacies restock their shelves daily and place orders with their distributors nearly every day. That, along with the invoices they constantly receive from distributors, would make it quite easy to detect escalated sales of flu medications.”

As for the drugs that can treat anthrax and other diseases associated with biological warfare, Alverson says she has already put in motion a statewide survey to determine what medications exist, in what quantities, and where they’re located. Such an effort has never before been mounted in the United States, to Alverson’s knowledge, and she has already received a great deal of interest from pharmacists in other states. “It’s a monumental task, to be sure, especially since there are more than 2,000 pharmacies—and 5,000 pharmacists—in Alabama,” she says. “But we’ve got to determine what we have on hand before we can attempt to predict what we’d need in case of an outbreak.”

Alverson has experience in dealing with disease outbreaks. As former director of pharmacy for the State of Virginia, she was on the front lines in an effort to prevent a major outbreak of swine flu in that state during the mid-1970s. “We’d never encountered anything like that before, and we had to vaccinate the whole state, which was a real learning experience for everyone involved.”

Preparing the Push Packs

In addition to determining Alabama’s current state of pharmacologic preparedness, Alverson is helping to establish an efficient means of locating and distributing medications in case an outbreak should occur. “If we find that we don’t have the necessary medications on hand,” she says, “the state health department would contact the federal government to send in what’s known as a ‘push pack,’ which is basically a fully equipped field hospital. These packs fill two military cargo planes, and they are stored and kept ready to fly at eight undisclosed locations around the country—the idea being that you can get them to any city within 12 to 24 hours.”

As comforting as it is to know that these push packs exist, the challenge of breaking them down and getting the medications into people’s hands is yet to be dealt with. “How should we go about doing that?” Alverson asks. “Would pharmacists be allowed to dispense medication without prescriptions? Would we want people venturing out into the community, running the risk of exposure? If we decided to deliver the meds straight to people’s doors, who would make the deliveries? These are just a few of the questions that we’ve got to address.

“And every question just seems to lead to another one,” she says.

Dealing with Dread

By definition, terrorism is designed to create fear. In the case of bioterrorism, the agents of fear—the weapons that terrify—are not even visible to the human eye. UAB environmental health scientist Steven Becker, Ph.D., has conducted numerous studies on how victims of biological, chemical, and radiological incidents have reacted to “invisible threats.”

“In a sense, terrorism involving weapons of mass destruction—including biological agents such as plague and anthrax—represents a combination of two broad characteristics, each of which is sufficient to create enormous stress,” Becker says. “First, such incidents involve agents that people are totally unfamiliar with; they are insidious and invisible, and that tends to trigger more concern than other kinds of danger.

“Second, such incidents are not mistakes or accidents, but calculated, intentional acts aimed by human beings at inflicting pain, injury, suffering, and death on other human beings,” he says. “This combination—of invisible, toxic agents coupled with the intent to harm—makes such acts of terrorism especially stressful.”

One reaction Becker has witnessed, both recently in the United States and in other countries after suspected or confirmed disease incidents, is panic-buying of medications. “This reaction is not altogether unexpected, since we’ve seen it after infectious disease outbreaks in the recent past,” he observes. “For example, following a 1994 plague outbreak in Surat, India, many people went to great lengths to purchase antibiotics. In that situation, health-care professionals were concerned that the indiscriminate use of antibiotics would reduce the effectiveness of treatment. So the run on the antibiotic Cipro that we’ve observed here is not a new phenomenon.”

Becker says the situation will likely improve once health officials make clear the risks of indiscriminate antibiotic use, “and once people come to understand that federal agencies have a large antibiotic stockpile and the means to rapidly get preventive medicine to those who may need it.”

The Armor of Awareness

Perhaps the strongest shield that can be wielded against bioterrorism is simple awareness—of the signals of trouble and the steps to take if those signals appear. The CDP has launched several projects to disseminate such information across the state and country, according to Program Manager Margaret Tresler, M.P.H. “We’ve already done presentations at local schools to give students a general understanding of what ‘bioterrorism’ means, and we hope to expand that function in the coming years,” she says. “We might send a microbiologist to a biology class, for instance—someone who could provide students with certain insights. We feel that, by fostering an understanding of the issues, we can dispel unnecessary fears.”

The center is also increasing awareness among health care professionals through a screensaver that can be loaded onto the computers of doctors, nurses, and various emergency-room personnel to help them spot symptoms of bioterrorism-associated diseases. Developed by the CDP with funding from the Agency for Healthcare Research and Quality, the screensaver provides detailed information through images and text about anthrax and smallpox—the effects of which most clinicians have never actually seen. “Our hope is that, by providing this information, we’ll help health-care professionals who encounter unfamiliar symptoms determine if what they’re seeing might be associated with anthrax or smallpox,” says Tresler.

Another education and outreach effort sponsored by the center is an annual, two-day conference that draws bioterrorism specialists from across the country to the UAB campus. Last year’s event, “The Statewide EMS and Disaster Preparedness Conference,” drew more than 400 people and was broadcast via satellite to some 2,000 more by the Alabama State Department of Public Health. The center has also launched an interactive Web site that can be accessed at [www.bioterrorism.uab.edu].

“I think one of the most important roles the center can play is bringing different groups of people together to exchange ideas—making them aware of what other groups are doing,” says Tresler. “We believe that UAB is in a prime position to be a leader in developing response plans to biological events, because we’ve already managed to bring together so many people with such a high degree of expertise.”

Terndrup, the center’s director, agrees. “The overriding issue, of course, is that of ‘preparedness’—being prepared for the possibility of any kind of attack,” he says. “Terrorists have demonstrated their intent to harm Americans, and we know now that they will go so far as to use biological agents. We also know that they have succeeded in their agenda of creating terror. People are understandably frightened of the microbes these terrorists are capable of releasing.

“But, with the army of experts we have in our center, there is much we can do—and are doing—to prepare.”

UAB Magazine

 

 

 

 

LINKS TO RELATED INFORMATION

Center for Disaster Preparedness
Department of Emergency Medicine
Department of Epidemiology & International Health

Comments? Questions? E-mail the editor:
Pam.Powell@VPUADV.UAB.EDU

 

 

 

 

WINTER 2002 ISSUE

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